Assay and single dose pharmacokinetics of a novel systemic acyl coenzyme A cholesterol O-acyltransferase inhibitor, RP 73163, in rat plasma using automated solid-phase extraction with high-performance liquid chromatography

J Chromatogr B Biomed Appl. 1994 Nov 4;661(1):119-31. doi: 10.1016/0378-4347(94)00322-x.

Abstract

RP 73163, (S)-2-[5-(3,5-dimethylpyrazol-1-yl)pent-1-yl]sulphinyl-4,5 diphenylimidazole (I), is a highly potent in vitro and in vivo inhibitor of acyl coenzyme A cholesterol O-acyltransferase (ACAT) (E.C. 2.3.1.26), and as such it has potential therapeutic use as a cholesterol lowering agent in man. A method has been developed for the extraction and assay of I from rat plasma, using a fully automated solid-phase extraction column (ASPEC) technique, coupled to a reversed-phase HPLC system with detection by native fluorescence. The method has been validated over the concentration range 10-500 ng/ml, with demonstrated linearity, precision and accuracy, the mean limit of detection being 6.6 +/- 1.3 ng/ml. Application of the method to the assay of samples following administration of the compound to male and female rats is reported, together with determined pharmacokinetic parameters.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Chromatography, High Pressure Liquid / methods*
  • Chromatography, High Pressure Liquid / standards
  • Drug Stability
  • Female
  • Imidazoles / administration & dosage
  • Imidazoles / blood*
  • Imidazoles / pharmacokinetics
  • Injections, Intravenous
  • Male
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Sterol O-Acyltransferase / antagonists & inhibitors*

Substances

  • Imidazoles
  • RP 73163
  • Sterol O-Acyltransferase